FDA Approves First Targeted Treatment for Patients With Cancer of Bile Ducts

“This approval demonstrates that while we continue to focus our efforts on addressing the COVID-19 coronavirus pandemic, FDA remains committed to the important work of reviewing treatments for patients with cancer and other serious conditions,” Richard Pazdur, MD, director of the FDA’s Oncology Center of Excellence (https://www.fda.gov/about-fda/fda-organization/oncology-center-excellence) and acting director of the Office of Oncologic Diseases (https://www.fda.gov/about-fda/center-drug-evaluation-and-research-cder/office-oncologic-diseases-ood) in the FDA’s Center for Drug Evaluation and Research, said. “With pemigatinib, we considered the observed efficacy results to be clinically meaningful and the overall risk to benefit assessment for patients with tumors harboring FGFR2 gene fusions and other rearrangements to be favorable, particularly when we considered that these patients have no other good options following first line treatment with chemotherapy.” 

Cholangiocarcinoma is a rare form of cancer that forms in bile ducts. The April 17 approval is for patients with cholangiocarcinoma that is locally advanced or metastatic and has a fusion or other rearrangement of the FGFR2 gene. 

At diagnosis, a majority of patients with cholangiocarcinoma have advanced disease with no surgical options. Until now, no FDA-approved therapies have been available for cholangiocarcinoma; a combination of chemotherapy drugs has been the standard initial treatment. FGFR2 fusions have been found in approximately 9%–14% of cholangiocarcinoma tumors. Pemigatinib is a tablet that works by blocking FGFR2 in tumor cells to prevent them from growing and spreading. 

Pemigatinib’s approval was based on the results of a clinical trial that enrolled 107 patients with locally advanced or metastatic cholangiocarcinoma with an FGFR2 fusion or rearrangement who had received prior treatment. During the clinical trial, patients received pemigatinib once daily for 14 consecutive days, followed by 7 days off, in 21-day cycles until the disease progressed or patients experienced an unreasonable level of side effects. To assess how well pemigatinib was working during the trial, patients were scanned every eight weeks. The trial used established criteria to measure how many patients experienced a complete or partial shrinkage of their tumors during treatment (overall response rate). The overall response rate was 36%, with 2.8% of patients having a complete response and 33% having a partial response. Among the 38 patients who had a response, 24 patients (63%) had a response lasting 6 months or longer and 7 patients (18%) had a response lasting 12 months or longer.    

The most common adverse reactions occurring in 20% or more of patients who received pemigatinib are hyperphosphatemia and hypophosphatemia, alopecia, diarrhea, nail toxicity, fatigue, dysgeusia, nausea, constipation, stomatitis, dry eye, dry mouth, decreased appetite, vomiting, joint pain, abdominal pain, back pain, and dry skin. Ocular toxicity was also reported.  

FDA granted the application priority review (https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/priority-review) and breakthrough therapy (https://www.fda.gov/patients/fast-track-breakthrough-therapy-accelerated-approval-priority-review/breakthrough-therapy) designation, which expedites the development and review of drugs that are intended to treat a serious condition, when preliminary clinical evidence indicates that the drug may demonstrate substantial improvement over available therapies. Pemigatinib received orphan drug (https://www.fda.gov/industry/developing-products-rare-diseases-conditions/designating-orphan-product-drugs-and-biological-products) designation, which provides incentives to assist and encourage the development of drugs for rare diseases. As a condition of the accelerated approval, the sponsor will complete and submit the results of a randomized trial demonstrating an improvement in progression-free survival or overall survival as a postapproval requirement.  

Healthcare professionals should report all serious adverse events suspected to be associated with the use of any medicine and device to FDA’s MedWatch Reporting System (https://www.accessdata.fda.gov/scripts/medwatch/index.cfm) or by calling 800-FDA-1088.